Refining our methodologies for assessing quadruplex DNA ligands; selectivity or an illusion of selectivity?

Regulation of transcription and replication by the tetrad patterns of DNA has drawn the attention of many scientists. In this perspective article, we discuss some disparaged parameters in the study of G-quadruplex structures (G4-tetrads). Besides, the implication of destabilization as a side-effect by these ligands on quadruplexes is explained. The lack of strict control of in vitro cell-free experiments in terms of ionic concentration, pH, epigenetic modifications, (macro)molecular crowding, and solvent effects is evident in many previous studies. The role of these factors in ligands binding and their possible effects in G-quadruplex structures are also represented.

Automated summary

This perspective article discusses overlooked parameters in the study of G-quadruplex structures and explains the destabilization effects of ligands on these structures. It also highlights the lack of strict control of various factors in in vitro cell-free experiments in previous studies.